title: The effect of celecoxib administration on the healing and neovascularization of colonic anastomosis in rats.
abstract: BACKGROUND
  The aim of this experimental study was to investigate whether the perioperative administration of the selective cyclooxygenase-2 inhibitor celecoxib affects the angiogenetic process and the healing of colonic anastomoses.
  
  
  METHODS
  Seventy-two male Wistar rats underwent colonic resection and anastomosis. Celecoxib (10 mg/kg/day-celecoxib group) or placebo (control group) was administered perioperatively. Rats of both groups were sacrificed on either the third or the seventh postoperative day and bursting pressures of the anastomoses were measured. Gelatine-degrading matrix metalloproteinases (MMPs) were identified with gelatine zymography, and proMMP-2 and vascular endothelial growth factor (VEGF) levels from both anastomotic site and tissue adjacent to the anastomosis were evaluated. Histologic evaluation of microvessels was performed by immunohistochemistry using an anti-CD34 monoclonal antibody.
  
  
  RESULTS
  Celecoxib did not significantly decrease anastomotic bursting pressures. Gelatin zymography revealed the presence of MMP-2, proMMP-2, and proMMP-9. MMP concentration was higher at the anastomotic tissue as compared with tissue distant to the anastomosis. Celecoxib resulted in a significant reduction in proMMP-2 levels at the anastomosis at both third and seventh postoperative day. VEGF levels from the anastomotic tissue were also found lower in the celecoxib group. Histological examination showed a celecoxib-induced reduction of newly formed CD34-stained vessels.
  
  
  CONCLUSIONS
  Although the perioperative administration of celecoxib resulted in suppression of angiogenesis in the newly formed anastomoses, bursting pressures remained unaffected and subsequently safety was not compromised.
authors.affiliation: Second Propedeutical Department of Surgery, School of Medicine, Hippokratio General Hospital, Aristotle University of Thessaloniki , Thessaloniki , Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Symeonidis
authors.forename: Eleni
authors.initials: E
authors.lastname: Papakonstantinou
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Psarras
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Ballas
authors.forename: Theodoros
authors.initials: T
authors.lastname: Pavlidis
authors.forename: Georgios
authors.initials: G
authors.lastname: Karakiulakis
authors.forename: Athanasios
authors.initials: A
authors.lastname: Sakantamis
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D000068579:Celecoxib; D003106:Colon / Q000098:blood supply / Q000378:metabolism / Q000601:surgery*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011312:Pressure; D011720:Pyrazoles / Q000009:adverse effects*; D011897:Random Allocation; D017208:Rats, Wistar; D013449:Sulfonamides / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D020782:Matrix Metalloproteinases; D000068579:Celecoxib